Endothelin receptor type A expression defines a distinct cardiac subdomain within the heart field and is later implicated in chamber myocardium formation
Endothelin receptor type A expression defines a distinct cardiac subdomain within the heart field and is later implicated in chamber myocardium formation
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DOI：
10.1242/dev.054015
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发表时间：
2010-11-15
期刊：
影响因子：
4.6
通讯作者：
Kurihara, Hiroki
中科院分区：
文献类型：
--
作者：
Asai, Rieko;Kurihara, Yukiko;Kurihara, Hiroki
鸟类和哺乳动物的心脏起源于两个不同的胚胎区域：早期分化的第一心脏区域和位于背部的第二心脏区域。目前尚不清楚心脏领域的这些细分何时以及如何划分为具有不同命运的区域。在这里，我们在小鼠中鉴定出以 A 型内皮素受体 (Ednra) 基因表达为标志的第一（新月形成）区域的亚群，该亚群通过独特类型的细胞行为对心室心肌做出贡献。 Ednra-lacZ/EGFP表达细胞出现在早期线性心管的腹尾流入区，会聚到中线，沿着外曲率向前移动并产生主要为左心室和两个心房的心室心肌。这种运动通过荧光染料标记和移植实验得到证实。 Ednra-lacZ/EGFP 表达亚群的特征是存在 Tbx5 表达细胞。 Ednra 缺失的胚胎心脏通常表现出心室壁发育不全、有丝分裂活性低以及 Tbx5 表达减少，而 Tbx2 表达则相反。相反，内皮素 1 刺激早期胚胎心脏中的 ERK 磷酸化和 Tbx5 表达。这些结果表明，早期 Ednra 表达定义了第一心区的一个子域，有助于心室形成，其中涉及内皮素 1/Ednra 信号传导。目前的发现提供了关于新月形（第一）心脏区域内的亚群如何通过时空定义的细胞运动来协调心脏形态发生的见解。
The avian and mammalian heart originates from two distinct embryonic regions: an early differentiating first heart field and a dorsomedially located second heart field. It remains largely unknown when and how these subdivisions of the heart field divide into regions with different fates. Here, we identify in the mouse a subpopulation of the first (crescent-forming) field marked by endothelin receptor type A (Ednra) gene expression, which contributes to chamber myocardium through a unique type of cell behavior. Ednra-lacZ/EGFP-expressing cells arise in the ventrocaudal inflow region of the early linear heart tube, converge to the midline, move anteriorly along the outer curvature and give rise to chamber myocardium mainly of the left ventricle and both atria. This movement was confirmed by fluorescent dye-labeling and transplantation experiments. The Ednra-lacZ/EGFP-expressing subpopulation is characterized by the presence of Tbx5-expressing cells. Ednra-null embryonic hearts often demonstrate hypoplasia of the ventricular wall, low mitotic activity and decreased Tbx5 expression with reciprocal expansion of Tbx2 expression. Conversely, endothelin 1 stimulates ERK phosphorylation and Tbx5 expression in the early embryonic heart. These results indicate that early Ednra expression defines a subdomain of the first heart field contributing to chamber formation, in which endothelin 1/Ednra signaling is involved. The present finding provides an insight into how subpopulations within the crescent-forming (first) heart field contribute to the coordination of heart morphogenesis through spatiotemporally defined cell movements.